Non-adherence to treatment is one of the most important problems in treatment of chronic illnesses. This condition is also valid for schizophrenia. In general, non-adherence in chronic illnesses is approximately 60%. The patients with schizophrenia and bipolar disorder do not believe that they are ill. They have lack of insight; therefore they reject to take medication. In treatment, perfect adherence to treatment is rare; non-adherence to treatment is a common condition. If the patient misses the drug dose small than 25%, he (she) is adherent. If the patient misses the drug dose between 25% and 65%, he (she) is partially adherent. If the patient misses the drug dose more than 65%, he (she) is non-adherent. Partially adherence to treatment is 25% in the first 10 days after discharge, 50% after one year, and 75% two years. If the adherence to treatment is increased, the ratio of remission is increased. If the patients do not use their medications regularly, some disadvantages are seen as follows: a) relapse ratio increases, the period and the number of admitted in hospital increases, suicide risk increases, the possibility of remission decreases, all of social functionalities go bad, substance use, and financial problems. Non-adherence to treatment can be dependent on characteristics of patient, environment, clinician, and medication. The causes of not taking medication can be those: lack of insight, lack of efficacy of treatment, lack of social support, worries about side effects, a poor doctor-patient relationship, cognitive losses, substance use, and comorbid psychiatric disorders. How are formed adherence to treatment between doctor and patient? The answers are as follows: a) Non-pharmacological approaches, b) pharmacological approaches, c) multidimensional approaches. Non-pharmacological approaches include motivational interview techniques and similar approaches, cognitive behavior therapy, and psycho-education approaches. The LEAP technique is a motivational interview technique. The phases of LEAP are as follows: Listen, Empathy, Agree, and Partnership. Cognitive behavior therapy has been neglected for schizophrenia because of some causes. However, it has been increased gradually that evidences about efficacy of cognitive behavior therapy in schizophrenia treatment. Psycho-education can apply both patients and their families. A psycho-education program must include those issues: the symptoms and the causes of schizophrenia; medications used for schizophrenia, their side effects, and their mechanisms; the manner of family; lawful rights and responsibilities; emergency conditions and follow-up. Pharmacotherapy is efficacy on schizophrenia treatment, especially on positive symptoms. Depot or long action antipsychotics increase the adherence to treatment, decrease suicide risk and the number of admitting in hospital. To provide and continue the adherence to treatment is suggested those strategies: to apply optimal antipsychotic treatment, to encourage the patients and their families for psycho-education, to determine the patients’ motivations, to treat substance abuse, to include family members in treatment process, to identify and remove the barriers to treatment. There are common problems seen in the adherence to treatment. These can be concerned with patients, patients’ relatives, presenting services. Multidimensional approach contains a good doctor-patient relationship, accepting the adherence problem, favorable antipsychotic treatment, forming a good atmosphere, applying motivational interview techniques and psycho-education.