Concerns have arisen during recent years over a possible link between suicide and medications used to treat several medical conditions, including depression, asthma, epilepsy, and smoking. The concern over the safety of these medications was sparked by data from postmarketing and retrospective analyses of clinical trials. However, clinical trials were not initially designed to measure suicidality, and this methodologic limitation weakens the ability to make causal conclusions. Postmarketing results also have methodologic limitations (such as the absence of control groups) that limit the ability to make causal conclusions. Postmarketing results are also misleading because each of the medical conditions involved is highly comorbid with depression. The risk of not treating these conditions with an active and effective medication may clearly outweigh the possible slight elevation of the risk of suicidal thoughts and behaviors. The decision to take a medication should be made in consultation with a physician and based upon considerations of the risks and benefits of the medication. Physicians and the public need accurate information on the suicide risks associated with medications to make informed treatment decisions. The most effective way to ascertain the true risk (or lack of risk) associated with a medication is to systematically and prospectively assess suicidal thoughts and behaviors in randomized, placebo-controlled clinical trials. If a medication is scientifically determined to increase the risk for suicidal thoughts and behaviors, then the risk needs to be accurately translated and communicated to physicians and patients. Physicians prescribing these medications will need to closely monitor and assess their patients for changes in mood and suicide risk throughout treatment and must be able to recognize when a patient needs specialized mental health care. Mental status changes can be appropriately monitored and managed. Some medical conditions, such as asthma and epilepsy, and some treatment goals, such as smoking cessation, have inherent increased risks for depression-and by extension, suicide-that necessitate accurate, ongoing assessment.