Plasma medication levels are useful because, compared with medication dosage, they are more highly correlated with medication concentration in the brain. They also assess medication adherence. Clozapine plasma levels are associated with both clozapine effectiveness and side effects. Clinician assessment of symptoms and side effects is the primary means of guiding treatment. However, there are circumstances when a clozapine level can be useful: when there are questions about medication adherence, when clozapine is less effective than expected, when there are more side effects than expected, when there are potential medication interactions, or when on a stable dosage (to establish a patient’s clozapine metabolism). Levels can also be useful when there are changes that affect P450 metabolism and blood levels, such as stopping or starting smoking around hospital admissions. Clozapine levels should be drawn at steady state and be a trough level. Levels are usually drawn more than 3 days after a patient is stable on a dose. Levels should be drawn about 12 hours after the last (usually nighttime) dose. Clozapine typically shows efficacy starting at levels above 250 ng/ml, though there has been efficacy below this level in some patients. The greatest efficacy is seen at levels higher than 350 ng/ml. The risk of seizures increases with levels above 1000 ng/L. When measuring clozapine levels, it can be helpful also to measure the level of norclozapine, the major active metabolite of clozapine. Norclozapine differs from clozapine in terms of side effects and has a longer half-life. Norclozapine level should be considered in conjunction with the clozapine level. When interpreting plasma levels, low clozapine levels can result from low dose, non-adherence, or rapid metabolism. If a clozapine level is high, check the patient for dose-related side effects. If there is clozapine toxicity, the patient should obtain urgent care that includes symptomatic treatment and assessment for serious problems such as cardiac arrhythmias. If the patient has no signs of toxicity, ensure that the result was a trough level, and consider whether there has been inhibition of P450 metabolic enzymes from changes in other medications or smoking. Monitor and recheck the level.