Fundamental biological processes require concurrent sharing of DNA by numerous motor proteins and complexes. Thus, collision, congestion, and roadblocks are inescapable on these busy “molecular highways.†The consequences of these traffic problems are diverse, resulting in complex cellular mechanisms to resolve threats to genome stability and ensure cellular viability. Here, we review the different types of events and the diverse consequences that an RNA polymerase may encounter during transcription. We also address advances in the field that facilitate in-depth investigation of intrinsic motor properties and multi-protein interactions and coordination, which are necessary to understand these complicated interactions. Together, these results provide mechanistic insights into how RNA polymerase successfully navigates its passage through crowded molecular highways. © 2018 Elsevier Ltd