During their life, cells are exposed to a wide variety of extracellular stimuli and have to develop appropriate biological responses. Signal transduction from the plasma membrane, which is in contact with the extracellular environment, to the nucleus, where gene expression is achieved, thus represents a fundamental process for the development and maintenance of life in organisms. Signalling pathways are extremely diverse and range from direct strategies, such as the steroid hormone receptor and JAK/STAT (signal transducers and activators of transcription) pathways, to multi-step strategies, such as the NF-kappa B (nuclear factor kappa B), PKA (protein kinase A) and Ras/MAPK (mitogen-activated protein kinase) pathways. In order to modulate gene expression, all these pathways must ultimately achieve nuclear localization. The mechanisms by which these varied signalling components cross the nuclear envelope are equally as diverse. However, despite the variety of the means used, cells have adopted several common themes for signal transduction, particularly interaction between proteins as a mean to transport the signal and phosphorylation as a post-translational modification carrying information. Finally, all signalling pathways have been conserved throughout evolution, inghlighting their advantage for cells. In mammals, proteins that participate in signal transmission represent a frequent target for mutations leading to tumor development. Unraveling signalling pathways thus represents an important step in the fight against cancer.