Treatment dissatisfaction and discontinuation continue to limit the long-term treatment of patients with schizophrenia. Schizophrenia comprises a wide spectrum of symptoms, including hallucinations, delusions, hostility, cognitive deficits, and depression and anxiety symptoms. Medication is often effective in the treatment of the positive and hostility symptoms of schizophrenia, but less effective on other symptoms of the disease i.e. negative, affective and cognitive symptoms. However, each one of these symptoms can impinge on the functionality of the patient and decrease their quality of life. For example, negative and affective symptoms may lead to low self-esteem and depression, while cognitive deficits are a major impediment to social and vocational rehabilitation. Even when therapy does address the spectrum of symptoms, often the side effects are severe and may contribute to patient non-compliance or withdrawal of therapy, as patients prefer to experience their disease symptoms rather than drug-induced adverse effects. Optimisation of long-term therapy to overcome these issues is now the challenge for antipsychotic therapy. Recent advances in the development of newer atypical antipsychotics bring us closer to achieving the correct balance between long-term efficacy, tolerability and patient function. Atypical antipsychotics have been shown to be effective for the treatment of positive, negative, affective and cognitive symptoms of schizophrenia. In addition, their advancing mechanisms of action provide advantages over the older agents in terms of long-term tolerability. The use of atypical agents to address the full range of psychotic symptoms with minimal adverse effects should ensure improved functionality and an improved patient quality of life in patients with schizophrenia: both can be regarded as positive reinforcers for long-term compliance.