This article reviews a variety of new nanoparticle/biomolecule assemblies for advanced electrical detection of proteins. Effective methods for the reliable and trace measurements of proteins are highly desired for facilitating the diagnosis of disease states and improving drug discovery. Ultrasensitive monitoring of biomolecular interactions of proteins is particularly challenging owing to the absence of PCR-like amplification protocols and their greater nonspecific binding to solid supports compared to oligonucleotides. Recent activity has led to innovative and powerful nanoparticle-based immunoassays and aptamer bioassays of proteins based on a variety of electrochemical detection schemes. The enormous signal enhancement associated with the use of nanoparticle amplifying labels and with the formation of nanoparticle-protein assemblies provides the basis for ultrasensitive electrochemical detection of proteins. Such protocols rely on the use of colloidal gold tags, semiconductor (quantum dot) tracers, carrier (amplification) nanomaterials, or magnetic (separation) beads, in connection to electrochemical stripping measurement of the metal tag. Remarkable PCR-like sensitivity has been achieved by coupling particle-based amplification units and various amplification processes. The use of nanocrystal tracers for designing electrochemical coding protocols for detecting multiple proteins will also be documented.