Before revision:  In this perspective, we aim to present and refine our definitions of selection and drift, as well as additional and important mechanisms that constrain evolution of the genome under certain contexts. We highlight that these processes need to be taken into account to correctly identify the targets of selection and stress that a major  field-wide goal in the future should be to quantify the absolute importance of these mechanisms.
After revision:  In this perspective, we first highlight the importance of the genomic and (a)biotic context of new mutations to identify the targets of natural selection. We then present mechanisms that may constrain the evolution of genomes and bias the inference of selection. We discuss these mechanisms within the two critical levels that they occur: the population level and the molecular level. We highlight that they should be taken into account to correctly identify the targets of selection and stress that a major field-wide goal in the future should be to quantify the absolute importance of these mechanisms.