Italian pharmaceutical policy has recently moved towards a “two lanes” approach, with regulation differing according to a drug’s patent status. This study analyses the Italian regulatory framework, focusing on policies related to “off-patent” drugs. Three main regulatory innovations have been examined: (i) generics, introduced in Italy for the first time in 1996; (ii) the reference pricing (RP) scheme, under which consumers pay part of the cost of high-priced products; (iii) pharmacists’ right of substitution, supported by a regressive margins system. The recent reforms are already producing some worthwhile results, at least in terms of competitive pressure on the (few) substances that run out of patent protection. However, further intervention could be required to achieve long-term sustainability.