The psychopathological dynamics in suicidality overcomes actual diagnostic distribution therefore pharmacotherapy has restricted role in overall prevention of suicidal behaviour among mentally ill and is demanding for clinician. This role is achieved through reduction and alleviation of suicidal risk with rational and individual pharmacotherapeutic approach emphasising effective, safe and tolerable treatment. The genetic and epigenetic factors, dysfunction of neurotransmitter, neuroendocrine system and stress response system has been determining for neurobiology of suicidality. Therefore, pharmacotherapeutic approach should be focused, not only on prevention and reduction of suicidality, but adjusted for general and diagnosis-specific risk factors. Suicidality represents trans-diagnostic issue, however making the correct diagnosis is of great importance. Identical group of psychiatric medications or even the same drug, could be palliating for suicidal behaviour in one diagnostic category and in other aggravating concerning suicidal ideations. Clinician should be reserved towards epidemiological studies about reducing suicidal rate due to increased consumption of antidepressants. Detailed data analysis showed there is no relevancy which antidepressants were given to specific patient, in what age and phase of illness. The FDA has issued warnings about possible increased risk of suicidal behaviour in children and adolescents when given antidepressant therapy. In general, serotoninergic drugs have neutral or mildly protective effect on potential suicidal behaviour while noradrenergic drugs may have activating effect or could even worsen suicidal ideation in certain phase of the illness. When given in appropriate dose and the right time, dual or noradrenergic antidepressants, could also have good protective impact on specific patient. In patients with bipolar disorder, antidepressive drug could be trigger for suicidal behaviour. Greater susceptibility when diagnosing bipolar disorder and broader usage of mood stablizing medications, alone or combined with other psychopharmacotherapy, has the significant role in suppression and elimination of suicidal behaviour. The lithium and sodium valproate are found to be particularly suitable for prevention and elimination of suicidal behaviour along with some other mood stabilizers. Pharmacotherapy of suicidality in patients with schizophrenia represents specific problem. Confirmed drug with anti-suicidal effect, clozapine, is not first choice medication and does not represent general solution for suicidality in schizophrenia. For clinician, the pharmacotherapy of suicidal behaviour consists of skilled individual and rational drug administration accompanied with appropriate psychotherapeutic support.