The negative consequences of biofilms are widely reported. A defining feature of biofilms is the extracellular matrix, a complex mixture of biomacromolecules, termed EPS, which contributes to reduced antimicrobial susceptibility. EPS targeting is a promising, but underexploited, approach to biofilm control allowing disruption of the matrix and thereby increasing the susceptibility to antimicrobials. Nanoparticles (NPs) can play a very important role as ’carriers’ of EPS matrix disruptors, and several approaches have recently been proposed. In this review, we discuss the application of nanoparticles as antibiofilm technologies with a special emphasis on the role of the EPS matrix in the physicochemical regulation of the nanoparticle–biofilm interaction. We highlight the use of nanoparticles as a platform for a new generation of antibiofilm approaches.