When studying the effects of climate change on eukaryotic organisms we often oversee a major ecological process: the interaction with microbes. Eukaryotic hosts and microbes form functional units, termed holobionts, where microbes play crucial roles in host functioning. Environmental stress may disturb these complex mutualistic relations. Macroalgae form the foundation of coastal ecosystems worldwide and provide important ecosystem services - services they could likely not provide without their microbial associates. Still, today we do not know how environmental stress will affect the macroalgal holobiont in an increasingly changing ocean. In this review, we provide a conceptual framework that contributes to understanding the different levels at which the holobiont and environment interact, and we suggest a manipulative experimental approach as a guideline for future research.