With the recent revolution in Molecular Biology and the deciphering of the Human Genome, understanding of the building blocks that comprise living systems has advanced rapidly. We have yet to understand, however, how the physical forces that animate life affect the synthesis, folding, assembly, and function of these molecular building blocks. We are equally uncertain as to how these building blocks interact dynamically to create coupled regulatory networks from which integrative biological behaviors emerge. Here we review recent advances in the field of biomechanics at the cellular and molecular levels, and set forth challenges confronting the field. Living systems work and move as multi-molecular collectives, and in order to understand key aspects of health and disease we must first be able to explain how physical forces and mechanical structures contribute to the active material properties of living cells and tissues, as well as how these forces impact information processing and cellular decision making. Such insights will no doubt inform basic biology and rational engineering of effective new approaches to clinical therapy.