Currently there is significant interest in understanding how macromolecular behavior observed in vivo might differ from that observed in vitro. One way to address this topic is through the use of molecular simulation methods. This talk will outline work in the Elcock group that has been aimed at developing and applying molecular simulation methods for modeling biological macromolecules in their intracellular environments. The principal focus of the talk will be on the use of Brownian dynamics methods to model flexible macromolecular models in a variety of scenarios. Time permitting, some ongoing large-scale Brownian and molecular dynamics simulations will also be described.