Proteins and enzymes are the macromolecular workhorses of living cells. In the cell, macromolecules interact with each other in specific ways, that allow the cell to perform its various functions. Macromolecular interactions are driven by the favourable change in free energy that occurs when molecules interact with their substrates, and much of what we know about the specific action of enzymes is in fact learned from biochemical assays that characterize these free-energy changes under standard in vitro conditions. However, simple biochemistry does not tell the complete story. Physical processes that occur in the cell can strongly modify the conditions under which molecular interactions take place and as such are an intergral part of cellular functioning. Likewise, physical processes that affect the mobility and spatial distribution of macromolecules in the cell are important to their biological activity, as they determine where and when these molecules are brought into contact with their substrates. This article first gives a short description of the interior of cells, the physical environment in which macromolecular interactions take place. Then the concept of free energy as a driving force behind biochemical reactions is introduced. Specific and nonspecific effects on the free-energy leels of interacting macromolecules in a cellular envrionmen are discussed. Finally, it focuses on processes that play a role in bringing molecules together in the cell. The principles of diffusion and directed transport driven by force generation in the cell are discussed.