This talk aims to raise some questions concerning the use of biomolecules as means to affect specific binding of particles and cells in the “bio-nano” field, with applications in materials assembly, sensors, diagnostics, and drug delivery. DNA pairing and antibody binding are widely used and highly effective, as long as nonspecific interactions are adequately suppressed: The strategy is that molecular-level specificity translates directly to specificity at larger length scales. Nature, however, does not typically rely on a single molecular pair to mate each type of cell pairs: multiple types of adhesion molecules are involved; the individual molecules may not be entirely specific, and outcomes are both highly selective and dynamic. This raises questions concerning our strategies for selective adhesion beyond the molecular scale: (1) How can multiple surface features be engineered for synergy (2) How can the same target molecules be employed different scenarios to achieve appropriate selectivity in each? And (3) How can synthetic interfacial constructs be engineered for dynamic selectivity and adhesion? The presentation shows our naïve efforts to design interfaces with targeted interactions that do not rely on the specificity of immobilized biomolecules.