OBJECTIVES: The pharmacies and wholesalers remuneration system in Portugal, with drugs dispensing, suffered structural changes after the approval of the Memorandum of Understanding (MoU), signed in May 2011 by the Portuguese Government and International Authorities, which intensified the degree of public pharmaceutical expenditure reduction requirements, in exchange for the financial assistance. The objectives of present study were: to provide an overview of these changes, its impact for pharmacies (2011-2014) and recent advances towards a more comprehensive remuneration system. METHODS: RESULTS: The fixed linear remuneration system was replaced in January 2012 by a regressive mark-up and minor fees system, per ex-factory price range (for pharmacies and wholesalers), determining the greatest change to the remuneration system during the last decades. In April 2014, a fixed fee and a variable mark-up were added in the lowest and highest price range. The pharmaceutical market was reduced by 876 million euro and NHS expense by 494 million euro over the past four years. The loss of pharmacy and wholesaler remuneration was 322.8 Million euro in the same period (37% of the overall market reduction), higher to the established objective of 50 million euro in the MoU. CONCLUSIONS: Changes in the legislation, accentuated after MoU implementation, caused a large reduction in remuneration of pharmacies, due to directly cuts in margins and indirectly decrease in prices. Several studies, published in the meantime, support the difficulties for the sector sustainability.