RNA polymerase is a ratchet machine that oscillates between productive and backtracked states at numerous DNA positions. Since its first description in 1997, backtracking - the reversible sliding of RNA polymerase along DNA and RNA - has been implicated in many critical processes in bacteria and eukaryotes, including the control of transcription elongation, pausing, termination, and fidelity. Most recently we found that backtracking also plays the central role in resolving conflicts between moving RNA polymerases and other molecular machines, such as active ribosomes, replisomes, and DNA repair enzymes. Macromolecule trafficking and cooperation involving these complexes establish new fundamental principles of gene regulation, genomic maintenance, and cellular adaptation to environmental changes.