With its detrimental impact on the global disease burden, clinical depression has recently gained momentum in health promotion research [1]. As the main cause of disability worldwide, the lack of timely treatment has been at the center of these investigations [2,31]. In order to effectively promote help-seeking, researchers have focused on finding the sweet spot where persuasive health communication principles and depressed cognition meet – with limited success (see Siegel et al. [3]). For example, emerging evidence suggests that prominent communication strategies can backfire in this vulnerable population due to the activation of negative self-beliefs [4]. Such findings highlight the urgent need for us to better understand the nature of depression, such that the likelihood of effective health promotion is increased [5]. One promising opportunity for translational science is the matching of health messages with the unique characteristics of depression [6,7]. The current research thus takes a closer look at how ‘stages’ of depression could impact the effectiveness of prominent communication strategies. A prominent framework often applied to normative populations, gain-and loss framing [8], focuses on positive (gain) and negative (loss) valence when promoting health behaviors. Given the negativity bias of depression [36,37], it remains unclear which type of valenced framing strategy would work best in this population. Two studies sought to test whether depressed individuals respond differently depending on depression severity. Moving away from generic health promotion messages, this research thus seeks to provide a starting point to effective health message customization based on ‘stages’ of depression.