Systemic Sclerosis (SSc) is a multisystem disease that affects the skin and internal organs (i.e., gastrointestinal tract, lung, heart, kidney and peripheral nervous system). In the early phase, lung involvement is characterized by interstitial inflammatory alterations that are detected by bronchoalveolar lavage analysis and high resolution computed tomography (ground glass). As the disease progresses, fibrotic changes become evident and the diffusing capacity for carbon monoxide (DLCO) is impaired. Cardiac involvement in SSc can be manifested as myocardial disease, pericardial disease, conduction system disease, or arrhythmias. Cardiac involvement is a poor prognostic factor, but the diagnosis may be late or missing because of the frequent discrepancy between clinical manifestations and the real cardiac involvement. For this reason, resort to all the available diagnostic procedures is recommended to achieve an early diagnosis. The motility disorders are a major feature of gastrointestinal involvement in SSc, striking any part of this system (especially esophagus and anorectal region). Kidney involvement and scleroderma renal crisis are now considered rare because of the introduction of ACE inhibitors. Some patients may develop myositis or erosive arthropathy that complicate enormously the joint retraction induced by skin fibrosis. The peripheral nervous system (PNS) is also targeted by SSc: a distal mononeuropathy of the median nerve is a frequent and early feature; autonomic nerve dysfunction (parasympathetic impairment and marked sympathetic overactivity) seems to be a fundamental etiologic factor linked to the development of microvascular, cardiac and gastrointestinal alterations. The whole approach to the SSc patient is very complex and must consider, at the same time, many organs and systems. Thus, a global vision of SSc patient is needed in order to assure an early diagnosis of specific organ involvement as well as early treatment. Systemic Sclerosis (SSc) is a multisystem disease, that affects the skin, the gastrointestinal tract, the lung, the heart and the kidney. The extent and severity of internal organ involvement are the more important factors influencing the disease outcome and prognosis in SSc. In recent years, it has become evident that early diagnosis and accurate staging of visceral involvement are fundamental for appropriate management and therapeutic approach to the disease. Diagnostic procedures for specific organ and system involvement are now more sensitive because of the continuous technological improvement and, mostly, because they take advantage of the studies carried out in other diseases by other medical branches. This review will consider briefly the most frequent and important organ involvement in SSc.