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With the coronavirus pandemic continue to unfold, mutate, and alter our lives, we are now more conscious of the presence of microbes around us. Socially distancing ourselves we wear masks, self-isolate if we are unwell and wash our hands at every opportunity. This talk introduces a way of living alongside the microbial realm where these invisible agents all around us are not "contaminants," or "pathogens" but companions, technological systems and designed spaces that generate more liveable "wicked"—or, irreducibly complex—homes and urban environments. This is possible as less than 1% of all known microbes are harmful to us, but they have drawn the most attention. To show what is possible I will share developments in actual proof-of principle prototypes from the Living Architecture project, the Active Living Infrastructure: Controlled Environment prototype, PHOENIX COST Action network activities and the Microbial Urbanism proposal, which are all microbial systems designed to process waste and generate new resources in cyclical systems of exchange. By designing the relatively frictionless exchange of biological materials between microbes and people takes place within our living spaces all around us, we gain access to a life-promoting metabolic economy between human and microbe that is capable of transforming our everyday activities into life-supporting actions. By focusing on our own microbiomes—the communities of microbes that help us digest our food, make our skin supple and even change our mood—we can use our role as propagators of the microbiome of the built environment—the communities of microbes that naturally inhabit our living spaces—to directly influence microbial activity in ways that can be designed to generate environmentally beneficial outcomes. To access these desired probiotic actions, a different approach to design is needed that engages strategies that are deployed by our immune systems that help establish a negotiated condition of mutual liveability. Most notably, the "pure" human subject at the heart of architectural design is decentred, so we can pay close attention to kinds of microbes we live alongside, recognise their diversity, understand their needs, and observe how they behave in different settings. Immunological strategies can help us fully engage the potential of this realm—not only to create healthier spaces during a pandemic but also mitigate urban environmental "harm" in untroubled times.