The use of antipsychotic medications entails a difficult trade-off between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. There is more variability among specific antipsychotic medications than there is between the first- and second-generation antipsychotic classes. The newer second-generation antipsychotics, especially clozapine and olanzapine, generally tend to cause more problems relating to metabolic syndrome, such as obesity and type 2 diabetes mellitus. Also, as a class, the older first-generation antipsychotics are more likely to be associated with movement disorders, but this is primarily true of medications that bind tightly to dopaminergic neuroreceptors, such as haloperidol, and less true of medications that bind weakly, such as chlorpromazine. Anticholinergic effects are especially prominent with weaker-binding first-generation antipsychotics, as well as with the second-generation antipsychotic clozapine. All antipsychotic medications are associated with an increased likelihood of sedation, sexual dysfunction, postural hypotension, cardiac arrhythmia, and sudden cardiac death. Primary care physicians should understand the individual adverse effect profiles of these medications. They should be vigilant for the occurrence of adverse effects, be willing to adjust or change medications as needed (or work with psychiatric colleagues to do so), and be prepared to treat any resulting medical sequelae.