Genome-scale models have developed into a vital tool for rational metabolic engineering. These models balance cofactors and energetic requirements and determine biosynthetic precursor availability in response to environmental and genetic perturbations. In particular, allocation of additional reducing power is an important strategy for engineering potential biofuel production from microbes. Many potential biofuel solvents induce biomolecular changes on the host organism that are not yet captured by genome-scale models. Here, methods of construction for several biomass constituting equations are reviewed along with potential changes to cellular composition with potential biofuels exposure. The biomass constituting equations of potential host organisms with existing genome-scale models are compared side-by-side to explore their evolution over the years and to explore differences that arise when these equations are compiled by different research groups. Genome-scale model simulation results attempt to address and provide guidance for further research into: (i) whether inconsistencies in the biomass constituting equations are relevant to predictions of solvent production, (ii) what level of detail is necessary to accurately describe cellular composition, and (iii) future developments that may enable more accurate characterizations of biomolecular composition.