Several recent analyses provide growing evidence of the influence of positive selection acting in the ancestors of modern humans. Additionally, the best way to explain current fluctuations in neutral variation across the genome is by including negative selection against a high rate of deleterious mutants. We suggest that explaining these predicted high deleterious mutation rates in humans could require the inclusion of additional factors, such as inbreeding and prezygotic selection, in addition to rank-order selection and fitness interactions among mutations. We also suggest that some forms of selection, rather than being relaxed in modern humans, are probably still acting and might intensify in the near future, and make some predictions about the next several millennia of human evolution.