Total hip and knee arthroplasties are some of the most common surgical procedures in the United States. While the majority of patients experience successful outcomes, there still remain a large number that undergo revision surgeries due to loosening of the implant, often secondary to septic or aseptic osteolysis. In this study, we sought to perform a comprehensive literature review to investigate underlying genetic causes that may predispose a patient to prosthesis failure. The following single nucleotide polymorphisms (SNPs) were found to have a statistically significant association with aseptic loosening: OPG-163A allele and A/A genotype, RANK+575T allele and T/T genotype, MBL-550 C allele and C/C genotype, MBL-550 G allele and G/G genotype, TNF-238A allele, TGF-β1 (29T→C) T/T genotype, MMPI-1 (rs5854) C allele, and C/C genotype and MMP-1 2G allele. Additionally, the IL-6 (-174G/-572G/-597A) haplotype was associated with a significant increase in osteolysis. A negative correlation with aseptic loosening was observed for SNPs of the IL-1Ra (rs5854) C allele and IL-2. SNPs that correlated with PJI/septic loosening were OPG-163A allele and A/A genotype, MBL-550 C allele and C/C genotype, MBL+54 G/G genotype, TLR9-1486 T/C, and C/C genotypes, IL1β-511T allele. The current understanding of both septic and aseptic periprosthetic osteolysis describes the process as predominantly inflammatory in origin and leading to enhanced osteoclast activity. As such, these studies sought to focus on SNPs located on genes encoding cytokines and receptors involved in the inflammatory process and in osteoclast differentiation. While the number of studies, sample size, and demographics are limiting factors, the results provide significant data indicating that an individual's genetics play a much more integral role in TJA outcomes than previously thought. We advocate for future studies to investigate further the influence of genetics on implant failures.