In Mixed Connective Tissue Disease (MCTD), features of various connective tissue disorders such as systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSSc), dermatomyositis/polymyositis (DM/PM), and occasionally Sjogren’s syndrome and rheumatoid arthritis (RA) can coexist and overlap. The picture is marked by the presence of high titer anti-U1 ribonucleoprotein (RNP) antibodies. Over the last 30 years since first described a lot of controversial studies have been published regarding the nature, the severity or the very existence of the condition. MCTD is not a benign condition easily responsive to treatment or without major complication as previously believed and every effort should be made from the start to identify the type and extent of organ involvement. Overall the mortality is not as high as in SLE but pulmonary hypertension and its cardiac complications are the major cause of death in MCTD and the patients should be monitored closely for its development and progression. This is a review of the clinical aspects and an update of the management of the main morbidities of MCTD.