There are many examples of the interaction between prokaryotes and eukaryotes. One such example is the polymicrobial colonization/infection by the various opportunistic pathogenic yeasts belonging to the genus Candida and the ubiquitous bacterium, Pseudomonas aeruginosa. Although this interaction has simplistically been characterized as antagonistic to the yeast, this review highlights the complexity of the interaction with various factors influencing both microbes. The first section deals with the interactions in vitro, looking specifically at the role of cell wall components, quorum sensing molecules, phenazines, fatty acid metabolites and competition for iron in the interaction. The second part of this review places all these interactions in the context of various infection or colonization sites, i.e., lungs, wounds, and the gastrointestinal tract. Here we see that the role of the host, as well as the methodology used to establish co-infection, are important factors, influencing the outcome of the disease. Suggested future perspectives for the study of this interaction include determining the influence of newly identified participants of the QS network of P. aeruginosa, oxylipin production by both species, as well as the genetic and phenotypic plasticity of these microbes, on the interaction and outcome of co-infection.