Conversely to the Pasteur's concept of transmissible diseases where an illness have a unique origin, based on the presence of a micro-organism focusing all fighting efforts, researchers and specialists working in the field of cardiovascular diseases had to integrate, as early as in the fifties, the idea of complexity and multifactoriality in their scientific and medical approaches. The characterisation of several determinants of cardiovascular diseases, mainly environmental, initiated with epidemiological studies and cohort follow-up, suggested that the impact of these factors, increasing or decreasing the risk varied among individuals, partly underlying population differences. A major question is to understand what does this susceptibility stand for and what are its physiopathological bases: lifestyles shared by the same group or genetic specificities of individual. The exponential development of genomics knowledge and techniques allows us to address this question in the context of genome complexity and helps to a better understanding of the occurrence, development and evolution of cardiovascular diseases. Beyond knowledge, genomics is modifying our approaches of treatment and prevention of cardiovascular diseases opening the way to new domains as pharmacogenomics and pharmacogenetics.