Somatic, gain-of-function mutations in ras genes were the first specific genetic 
alterations identified in human cancer about 3 decades ago. Studies during the 
last quarter century have characterized the Ras proteins as essential components 
of signaling networks controlling cellular proliferation, differentiation, or 
survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently 
found in human tumors are known to throw off balance the normal outcome of those 
signaling pathways, thus leading to tumor development. Oncogenic mutations in a 
number of other upstream or downstream components of Ras signaling pathways 
(including membrane RTKs or cytosolic kinases) have been detected more recently 
in association with a variety of cancers. Interestingly, the oncogenic Ras 
mutations and the mutations in other components of Ras/MAPK signaling pathways 
appear to be mutually exclusive events in most tumors, indicating that 
deregulation of Ras-dependent signaling is the essential requirement for 
tumorigenesis. In contrast to sporadic tumors, separate studies have identified 
germline mutations in Ras and various other components of Ras signaling pathways 
that occur in specific association with a number of different familial, 
developmental syndromes frequently sharing common phenotypic 
cardiofaciocutaneous features. Finally, even without being a causative force, 
defective Ras signaling has been cited as a contributing factor to many other 
human illnesses, including diabetes and immunological and inflammatory 
disorders. We aim this review at summarizing and updating current knowledge on 
the contribution of Ras mutations and altered Ras signaling to development of 
various tumoral and nontumoral pathologies.