Virus capsids, specialized protein shells that encase the genome of viral pathogens, play critical roles in regulating viral infection, and are, thus, of great pharmacological interest as drug targets. In particular, small-molecule drugs (typically <900 Da) represent a promising antiviral strategy, and a number of such compounds have been developed to inhibit virus capsids by interfering with their assembly and uncoating processes. Importantly, to explain the mechanisms by which drugs disrupt capsid function, as well as to successfully design novel therapeutics, the interactions of drug molecules with their capsid targets must be studied at full chemical detail. Toward this end, all-atom molecular dynamics simulations are emerging as an essential technique to investigate the effects of small-molecule drugs on capsid structure and dynamics. Research presented in a recent Perspective applying simulations in NAMD to study drug-bound hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) capsids suggests the types of valuable chemical and physical information computational approaches can reveal, and underscores the importance of simulating, not isolated capsid proteins, but functional assemblies up to the level of complete capsids. Notably, through analysis with VMD, the study found that binding of the drug HAP1 to the HBV capsid causes global structural changes that subtly alter the overall capsid shape, including a flattening of capsid curvature. Further, the study found that the binding of the drug PF74 to the HIV-1 capsid imposes rigidity and causes shifts in allosteric communication pathways connecting distant regions of the capsid protein. The authors of the Perspective anticipate that many other such exciting discoveries regarding virus capsid function and their use as drug targets lie just ahead on the horizon, and molecular dynamics simulations will drive these discoveries pending a series of notable advancements in computational methodology.