The Nobel prize in chemistry 2004 was given to Aaron Ciechanover, Avram Hershko and Irwin Rose for their discovery of the ubiquitin mediated proteolysis. Years of research have shown that the ubiquitin pathway plays a crucial role in the cellular metabolism and its regulation. These scientists together with Alexander Varshavsky have identified the most important elements of this pathway as well as their interactions. The ubiquitin pathway degrades intracellular proteins with an ubiquitin chain being the tag that marks proteins assigned for degradation. This process is mediated by ubiquitin-activating enzyme (El), ubiquitin-conjugating enzymes (E2) and ubiquitin-protein ligases (E3). Mono-ubiquitination and deubiquitination play a classic regulatory role in numerous processes including cell-cycle, transcription, translation, DNA repair, stress response etc. This article tries to summarize current knowledge on the molecular basis of the ubiqutin pathway. (Fig. 1, Ref. 52.)