Bacterial chondronecrosis with osteomyelitis is the most important cause of lameness in broilers. This is important to poultry production, as it poses animal welfare issues, and causes a significant loss in revenue. The remediation of this disease requires the study of its etiology with fitting models and evaluating preventatives. The research reported herein covers genomic virulence analysis of BCO isolates, mainly Staphylococcus aureus, and Escherichia coli retrieved from lame birds. We found that S. aureus isolates were closest to chicken strains in Europe but may have been in the Arkansas area for a decade. Phylogenomics suggest our S. aureus is restricted to poultry, while the E. coli spans various hosts. This dissertation includes the analyses of mainly BCO isolates to determine virulence using the embryo lethality assay. Human S. aureus was the most lethal to layer and broiler embryos. Staphylococcus agnetis 908 that may induce lameness to \u3e50% did not show virulence. This inconsistency among others compelled us to offer that embryo lethality assay may not be an effective tool for estimating the pathogenicity of BCO isolates. Furthermore, research reported herein covers the investigation of the feed additive Availa-ZMC for lameness reduction potential in broilers using litter and wire-flooring models for inducing lameness. Availa-ZMC (a mixture of organic trace minerals) resulted in a reduction of lameness by 20% in the wire-flooring model, and 25% in the challenge on litter flooring model. Finally, this dissertation reports on a Typhoid-Mary experiment in broilers raised on the wire flooring to determine whether broilers challenged with S. agnetis can transmit the bacterium to birds in the same pen thereby spreading BCO and lameness. The Typhoid Mary experiment shows that young broilers exposed to S. agnetis at an early age harbor the bacterium and if mixed with unexposed birds 10 days later can transmit the bacterium to their pen mates