Research in novel materials has been extremely active over the past few decades, wherein a major area of interest has been nanoparticles with special optical properties. These structures can overcome some of the intrinsic limitations of contrast agents routinely used in medical practice, while offering additional functionalities. Materials that absorb or scatter near infrared light, to which biological tissues are partially transparent, have attracted significant attention and demonstrated their potential in preclinical research. In this review, we provide an at-a-glance overview of the most recent developments in near infrared nanoparticles that could have far-reaching applications in the life sciences. We focus on materials that offer additional functionalities besides diagnosis based on optical contrast: multiple imaging modalities (multimodal imaging), sensing of physical and chemical cues (multivariate diagnosis), or therapeutic activity (theranostics). Besides presenting relevant case studies for each class of optically active materials, we discuss their design and safety considerations, detailing the potential hurdles that may complicate their clinical translation. While multifunctional nanomaterials have shown promise in preclinical research, the field is still in its infancy; there is plenty of room to maximize its impact in preclinical studies as well as to deliver it to the clinics.