The aim of this review is to describe the theoretical background lying behind the solid drug mechanochemical activation by cogrinding pointing out its advantages and drawbacks. A brief historical introduction precedes the discussion about the mechanisms leading to solid drug activation. This allows to clarify the concept of solid activation whose main effect is to improve drug solubility and, thus, drug bioavailability. Then, the attention is focused on the experimental tools used to evaluate drug activation before the in vivo use. This, of course, permits to properly modulate the milling conditions (milling time, mill revolution speed, drug/carrier ratio and so on) in the light of the optimisation of milling process and activated system properties. Thereafter, the discussion shifts on the different kinds of mills that can be used and on mills classification based on the energy transferred to the materials. Fundamental tool to perform this task is the mathematical modelling of mill dynamics that is here shown for different mills kinds. Finally, some examples of activated systems performance both in vitro and in vivo are presented and discussed. In conclusion, mechanochemical activation improves drug bioavailability. Interestingly, this activation does not require the use of solvents whose elimination from the activated product can be difficult and expensive but a relatively simple mechanical treatment. On the other hand, this approach, usually, works only for poorly water soluble drugs (solubility <100 microg/mL) that do not exhibit permeability problems.