The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of modifying a surface on a droplet microactuator is provided, wherein the method includes executing one or more droplet operations to bring a droplet comprising a surface-modifying agent into contact with the surface. According to another embodiment, a droplet microactuator is provided and includes a sample or reagent immobilized on a surface thereof and arranged such that a droplet on the droplet microactuator may contact the surface. According to yet another embodiment, a method of removing a substance from a surface to which the substance is bound is provided, the method including conducting one or more droplet operations to contact a droplet with the surface, the droplet comprising a solution for eluting the substance from the surface