Among luminescent nanostructures actively investigated in the last couple of decades, rare earth (RE3+) doped nanoparticles (RENPs) are some of the most reported family of materials. The development of RENPs in the biomedical framework is quickly making its transition to the ∼800 nm excitation pathway, beneficial for both in vitro and in vivo applications to eliminate heating and facilitate higher penetration in tissues. Therefore, reports and investigations on RENPs containing the neodymium ion (Nd3+) greatly increased in number as the focus on ∼800 nm radiation absorbing Nd3+ ion gained traction. In this review, we cover the basics behind the RE3+ luminescence, the most successful Nd3+-RENP architectures, and highlight application areas. Nd3+-RENPs, particularly Nd3+-sensitized RENPs, have been scrutinized by considering the division between their upconversion and downshifting emissions. Aside from their distinctive optical properties, significant attention is paid to the diverse applications of Nd3+-RENPs, notwithstanding the pitfalls that are still to be addressed. Overall, we aim to provide a comprehensive overview on Nd3+-RENPs, discussing their developmental and applicative successes as well as challenges. We also assess future research pathways and foreseeable obstacles ahead, in a field, which we believe will continue witnessing an effervescent progress in the years to come.