The life cycle of endogenous retroviruses (ERVs), also called long terminal repeat (LTR) retrotransposons, begins with transcription by RNA polymerase II followed by reverse transcription and re-integration into the host genome. While most ERVs are relics of ancient integration events, “young” proviruses competent for retrotransposition—found in many mammals, but not humans—represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post-transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that LTR sequences derived from distantly related ERVs have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of ERV LTRs acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for LTR exaptation in developmental and tissue-specific gene regulation. Solitary long terminal repeats (LTRs) have been frequently domesticated into gene regulatory elements in mammals. Here, Thompson et al. evaluate the features of LTRs that account for the prevalence of this phenomenon and highlight recent studies providing insight into the molecular mechanisms that influence the exaptation of LTRs.