Many serious adverse physiological changes occur during spaceflight. In search for underlying mechanisms and possible new countermeasures, many experimental tools and methods have been developed to study microgravity caused physiological changes, ranging from in vitro bioreactor studies to spaceflight investigations. Recently, genomic and proteomic approaches have gained a lot of attention, after the major scientific breakthroughs in the field of genomics and proteomics, it is now widely accepted to understand biological processes. Understanding gene and/or protein expression is the key to unfolding the mechanisms behind microgravity induced problems, and ultimately, finding effective countermeasures to spaceflight-induced alterations. Significant progress has been made in identifying the genes/proteins responsible for these changes. While many of these genes and/or proteins were observed to be either up-regulated or down-regulated, however, there are no large scale genomics and proteomics studies have been published so far. This review aims at summarizing the current status of microgravity related genomics and proteomics studies and stimulating large scale proteomics and genomics research activities.