Genetic research in Psychiatry is viewed by clinicians with both hope and curiosity sometimes mixed with disillusionment. Indeed, in the last 30 years many results have not been confirmed and clinical applications are still missing. However recent findings suggest that we are at the beginning of a new era. A set of variants within neuroplasticity and inflammation genes have been identified as a valid basis for both bipolar disorder and major depression. Similarly, a set of genes has been identified as a liability factor for response and tolerability to antidepressants and the first clinical applications are already in the market. However, some caution should be applied until definite findings are available.