What Does USMLE Step 1 Cover? A Breakdown of the Content

If you’ve ever opened a Step 1 review book and felt a sudden urge to close it and take a three-hour nap, you aren’t alone. The sheer volume of information can feel like trying to map the entire ocean with a magnifying glass.

The most common question we get from students starting their prep is: “Do I really need to know every single enzyme in the Krebs cycle?” (Spoiler: Probably not, but you definitely need to know the ones that cause disease when they break).

Understanding exactly what USMLE Step 1 covers is the first step toward working smarter, not harder. You don't need to know everything—you need to know what the NBME actually cares about.

The Two Pillars: Systems vs. Disciplines

The USMLE doesn't just test subjects in isolation. Instead, it weaves together disciplines (like Physiology or Microbiology) and organ systems (like the Cardiovascular or Renal systems).

1. The Disciplines (The "How")

These are the scientific "rules" of the human body. The exam is broken down into these core areas:

• Pathology (45–52%): By far the most tested discipline. If you don't understand how tissue looks and behaves under stress or disease, you're going to have a bad time.
• Physiology (26–34%): This is the "how it works" part. Expect lots of arrows and "if X increases, what happens to Y?" questions.
• Pharmacology (15–22%): Focuses on mechanisms of action, side effects, and drug-to-drug interactions.
• Biochemistry & Nutrition (14–24%): No longer just rote memorization; you must apply these pathways to clinical scenarios (e.g., "A child presents with a musty odor...").
• Microbiology & Immunology (10–15%): Knowing your bugs, your drugs, and how the body fights back.
• 2. The Organ Systems (The "Where")

The exam also categorizes questions by the systems they affect. While the percentages vary slightly each year, here is the general spread:

• General Principles (12–15%): Foundational concepts that apply across all systems (like cell biology and genetics).
• Cardiovascular System (5–9%)
• Gastrointestinal System (5–9%)
• Respiratory System (5–9%)
• Renal & Urinary System (4–6%)
• Reproductive & Endocrine Systems (6–10%)

Strategic Insight: The "High-Yield" Reality

It’s a trap to think that all topics are created equal. In the Pass/Fail era, your goal is efficiency.

Real talk: You could spend three days mastering the intricacies of every single rare genetic mutation, or you could spend those three days mastering Autonomic Pharmacology and Cardiovascular Physiology. One of those options will gain you significantly more points on test day.

The USMLE Step 1 covers a mile-wide range of topics, but it only goes an inch deep on the "fluff" and very deep on the "high-yield" mechanisms. If a topic is common in a clinical setting (like Diabetes or Hypertension) or represents a "classic" medical school concept (like Lysosomal Storage Diseases), it's fair game and likely to show up.

Quality Over Quantity

The biggest mistake students make is trying to memorize the entire 600+ pages of First Aid without actually understanding the underlying mechanisms. The USMLE tests application. They won't ask you to name an enzyme; they'll describe a patient and ask you what the product of that enzyme's reaction would be in a healthy person.

If you can explain the why behind a symptom, you've mastered the content. If you're just memorizing "A leads to B," you're at risk of being tripped up by a slightly different question format.

Master the Content Without the Fluff

We know that looking at the USMLE content outline is overwhelming. That’s why we created a way to digest all this information without the "brain fog" that comes from dense textbooks.

Our Complete USMLE Step 1 Bundle takes everything Step 1 covers and distills it into high-yield, visually organized notes and guides. We’ve already done the hard work of separating the "must-knows" from the "nice-to-knows," so you can focus on securing your pass and moving on to your clinical rotations.

Don't get lost in the details. Focus on what matters and crush Step 1.