Schizophrenia and psychotic disorders represent psychiatric disease patterns characterized by remarkable impairment arising from alterations in cognition, perception, and mood. Although these severe illnesses have been known for more than 100 years, psychopharmacological treatment of their characteristically broad spectrum of symptoms as well as patients' quality of life, compliance, and time to relapse still remain a challenge in everyday clinical practice. In the following, we will provide a brief synopsis of first-generation antipsychotics (FGAs) followed by a detailed description of current second-generation antipsychotics (SGAs) along with their effects and side effects to evaluate unmet needs in the treatment of schizophrenia and psychotic disorders.Overall, drug profiles differ concerning their efficacy, associated side effects, cost, and mechanism of action. Thus, a shared decision-making process taking all these factors into account is necessary to develop an effective treatment based on currently approved compounds. To date, however, the spectrum of options is limited and only serves a limited proportion of patients. In addition, certain symptoms do not respond well to currently available strategies or respond only at the price of considerable side effects leading to reduced compliance and adherence in a substantial number of cases.Unmet needs in the field of antipsychotic treatment are found in a wide range of areas starting from efficacy, safety and tolerability, compliance and adherence, and continuing to stage-dependent and more personalized approaches.