Compared to other cells, sperm undergo dramatic remodeling of their chromatin during late spermiogenesis in which approximately 95% of histones are removed and replaced with protamines. Despite this large-scale remodeling, key developmental genes, some miRNA genes, and imprinted genes retain their association with histone. The developmental genes have a unique epigenetic signature, termed bivalency, that poises the genes for embryonic activation. Anomalies in that epigenetic poising signature, either in the form of DNA methylation aberrations, improper protamination, or altered histone modifications, are associated with infertility and reduced embryogenesis capability. Additionally, some small noncoding RNAs are retained, while others are actively added to the sperm and appear to affect embryogenesis. Therefore, initial studies have begun to formulate pathways by which the sperm epigenome can be used as a diagnostic tool in the clinic. While in their infancy, these assays likely portend improved diagnostics and added information for patients and clinicians. Recent studies also highlight the possibility that the sperm epigenome can be used to evaluate lifestyle and environmental risks to the patient and potentially to the offspring.