Clozapine is effective for treatment-refractory schizophrenia, but it shows several severe and potentially life-threatening side effects such as agranulocytosis, myocarditis, and cardiomyopathy. Therefore, it is necessary to minimize the risk of clozapine and maximize its effectiveness by monitoring of safety. White blood cell monitoring is mandatory in many countries, but the clozaril patient monitoring service (CPMS) in Japan additionally requires blood sugar monitoring for adverse metabolic events. Aside from the side effects described above, clozapine can cause various adverse events including constipation, paralytic ileus, seizure, orthostatic hypotension, syncope, hypersalivation, aspiration pneumonia, and oversedation. Consequently, it is important to conduct safety monitoring other than CPMS-based in routine clinical settings. Regarding CPMS as one model for safety monitoring, herein we discuss how to monitor the side effects induced by psychotropic agents. Although the choice of monitoring method depends on which drug is used, routine monitoring of parameters such as serum drug concentration, full blood count, biochemistry test, ECG, EEG, chest and abdominal X-P, body weight, body temperature, pulse, and blood pressure is necessary for early detection and prevention of severe adverse events. Further examinations are necessary to reach consensus on how often monitoring is required. Psychiatrists must devote more attention not only to multidimensional psychiatric symptoms but also to physical conditions. Psychiatrists can show themselves at their best in holistic medical care only by administering balanced psychiatric and physical examinations.