This talk will present the results of two recent studies of the deformation of hcp metals, results from the combination of modern first-principles computational methods with advanced experimental characterization techniques. The first topic concerns the origins of the intense hardening effect of dilute oxygen solutes in pure hcp titanium, arising from strong interactions with screw dislocations in this material. It is demonstrated that distortion of the interstitial sites at the screw dislocation core creates a very strong but short-range repulsion for oxygen that is consistent with experimental observations, and leads to a highly effective mechanism for strengthening. The second topic concerns the unique mechanical deformation properties of hcp rhenium, which is dominated by twinning at room temperature. Calculations reveal anomalously low values of the twin boundary energies in this material, which are linked to atomic geometries in the interface similar to those observed in bulk tetrahedrally close packed phases. The results establish a link between twin boundary energetics and the theory of bulk structural stability in transition metals that may prove useful in controlling mechanical behavior in alloy design more generally.