Non-ischemic dilated cardiomyopathy (NI-DCM) represents a specific etiology of systolic heart failure that usually affect young individuals with a genetic background in up to 40% of cases. Behind the term NI-DCM there is a spectrum of different diseases, and an accurate etiological classification appears pivotal for the clinical management and prognostic stratification of these patients. In the last years the prognosis of NI-DCM patients dramatically improved thanks to the progresses in medical treatment/ device therapy and earlier diagnosis especially in familial context. In this review we summarize the actual state of art in the management of these patients. In the era of precision medicine, a lot of progresses have been made to expand our knowledge on the management of NI-DCM patients. A complex interaction between genotype and external triggers is the main determinant of the clinical phenotype in NI-DCM, and a lot of efforts must be done by clinicians to systematically rule out all the possible causes involved in the pathogenesis. Progresses in cardiac imaging and familial screening led us to detect subtle abnormalities in the initial phase of the disease and also helped us to furtherly stratify the prognosis and arrhythmic risk of these patients. It is plausible that a more precise etiological classification will be needed in the near future. NI-DCM contains a spectrum of different diseases. Proper etiological classification, early diagnosis and strict follow-up are essential to tailor care of these patients.