A principal challenge facing the development and scaling of biomolecular computers is the design of physically well-motivated, experimentally validated simulation tools. In particular, accurate simulations of computational behavior are needed to establish the feasibility of new architectures, and to guide process implementation, by aiding strand design. Key issues accompanying simulator development include model selection, determination of appropriate level of chemical detail, and experimental validation. In this work, each of these issues is discussed in detail, as presented at the workshop on simulation tools for biomolecular computers (SIMBMC), held at the 2003 Congress on Evolutionary Computation. The three major physical models commonly applied to model biomolecular processes, namely molecular mechanics, chemical kinetics, and statistical thermodynamics, are compared and contrasted, with a focus on the potential of each to simulate various aspects of biomolecular computers. The fundamental and practical limitations of each approach are considered, along with a discussion of appropriate chemical detail, at the biopolymer, process, and system levels. The relationship between system analysis and design is addressed, and formalized via the DNA Strand Design problem (DSD). Finally, the need for experimental validation of both underlying parameter sets and overall predictions is discussed, along with illustrative examples.