The replication and transcription machinery concurrently use the same DNA region as template so that the machineries inevitably collide with each other in the manner of either head-on or co-directional. Both head-on and co-directional collisions lead to a pause of replication fork, thereby DNA damage and genome instability. The head-on collision is more detrimental than the co-directional in respect of genome integrity. Here we review the resolving mechanisms and evolutionary impact of the replication-transcription collisions. The rate of nonsynonymous (amino-acid-changing) mutations on the lagging is higher relative to that on the leading strand and the high frequency mutagenesis in genes on the lagging strand is dependent on transcriptions and gene sizes, thus faster adaptive mutations occur on the lagging strand. Highly transcribing of head-on oriented genes increases the mutation rates responding to stress during active replication. It is likely that the replication-transcription collision no matter in the head-on or co-directional mode is a driving force for adaptive evolution.