Traditionally, Schizophrenia was considered to be a severe psychiatric disorder, with a chronic course and an unfavorable outcome. Throughout history, there has been incidence of Schizophrenia, roughly one percent of the population, consistently, in every culture. It is generally acknowledged that Schizophrenia has multifactorial etiology, with multiple susceptibility genes interacting with environmental insults to yield a range of phenotypes in the Schizophrenia spectrum. The discovery of antipsychotics in the 1950s revolutionized the treatment of Schizophrenia and focused on the positive symptoms. By the 1960s, however, it became evident that the reduction in positive symptoms did not lead to recovery from Schizophrenia and did not significantly improve the functional outcome. The advent of the novel antipsychotics during the last 15 years represents a significant improvement over the effectiveness of conventional antipsychotics. These agents are, however, not a magic bullet and bear their own side effects, such as weight gain, diabetes, hyperprolactinemia, and QTc prolongation. Nevertheless, at this point, they seem to be more effective and safer than the conventional antipsychotics. Moreover, advances in the treatment of Schizophrenia have been and continue to be urgently needed.