In particular, Bertolami studied baryogengesis, the cosmological constant problem and its connection with the equivalence principle, the generalized Chaplygin gas model of unification of Dark Energy (to explain the cosmic acceleration) and Dark Matter (to explain the flattening of the rotation curves of galaxies) and some Modified models of gravity with non-minimal coupling between curvature and matter. He has also worked on the Pioneer Anomaly, which was shown to be most likely due to on-board thermal effects and reflection of the generated radiation. Most recent work concerns extensions of quantum mechanics based on phase-space noncommutativity.