In retrospect, 2014 will be seen as the year in which idiopathic pulmonary fibrosis (IPF) therapies came of age. Treatment effects reported previously were inconclusive with regard to both pirfenidone (two positive studies [1, 2] and a negative study [2]) and nintedanib (a single phase II study in which trends were marginal due to under-powering [3]). The ASCEND pirfenidone trial [4] and the two INPULSIS nintedanib trials [5] ended uncertainty. The two agents appear remarkably similar in both tolerability and efficacy, with a 50% reduction in forced vital capacity (FVC) decline. Whither now? No biomarker data exist to indicate that either agent might be more efficacious in individual patients. Initially, the routine use of these therapies is likely to be sequential, with one agent replaced by the other when side-effects are problematic or treatment failure is evident, however this is defined. In the longer term, combinations of pirfenidone and nintedanib appear attractive in principle, based both on the possibility of synergy in a disease in which there is a multiplicity of coactivated pathways, and also on precedence in other lung diseases including asthma, chronic obstructive pulmonary disease, lung cancer and pulmonary artery hypertension [6]. However, the road to combination regimens in IPF is likely to have many twists and turns. Two particular problems need to be addressed, even supposing that additive or synergistic benefits exist (something that has yet to be established). Tolerability issues are important, as both agents give rise to significant gastrointestinal side-effects. It should also be understood from the outset that demonstrating efficacy will not be straightforward. Intense multinational activity was needed to show treatment benefits against placebo arms characterised by FVC declines approximating 220 mL·year^–1. The treatment advances of 2014 sound the death knell of placebo-controlled evaluation in IPF: it seems inevitable that combination regimens will be compared with monotherapy. The rate of FVC decline of approximately 110 mL·year^–1 in patients receiving either pirfenidone or nintedanib will pose major challenges with regard to powering future trials [6]. The current issue of the European Respiratory Journal (ERJ) features two studies that are highly relevant to tolerability and study design issues.