In 1995, the year the first cancer nanomedicine, Doxil, was approved by the Food and Drug Administration (FDA), only 23 manuscripts appeared in a PubMed search for "nanoparticles for cancer" keywords. Now, over 25 000 manuscripts can be found using those same keywords, yet only 15 nanoparticle-based cancer nanomedicines are approved globally. Based on the clinicaltrials.gov database, a total of 75 cancer nanomedicines are under clinical investigation involving 190 clinical trials summarized here. In this Account, we focus on cancer nanomedicines that have been approved or reached clinical trials to understand this high attrition rate. We classify the various nanomedicines, summarize their clinical outcomes, and discuss possible reasons for product failures and discontinuation of product development efforts. Among ongoing and completed clinical trials, 91 (48 completed) are phase 1, 78 (59 completed) phase 2, and 21 (11 completed) phase 3. The success rate of phase 1 trials has been high-roughly 94%. Of those phase 1 trials with identified outcomes, 45 showed positive safety and efficacy results, with only one negative result (low efficacy) and two terminated due to adverse reactions. In some cases, findings from these trials have not only shown improved pharmacokinetics, but also avid drug accumulation within tumor tissues among active-targeting nanoparticles, including BIND-014, CALAA-01, and SGT-94. However, the success rate drops to ∼48% among completed phase 2 trials with identified outcomes (31 positive, 15 negative, and 4 terminated for toxicity or poor efficacy). A majority of failures in phase 2 trials were due to poor efficacy (15 of 19), rather than toxicity (4 of 19). Unfortunately, the success rate for phase 3 trials slumps to a mere ∼14%, with failures stemming from lack of efficacy. Although the chance of success for cancer nanomedicines starting from the proof-of-concept idea in the laboratory to valuable marketed product may seem daunting, we should not be discouraged. Despite low success rates, funding from the government, foundations, and research organizations are still strong-an estimated > $130 M spent by the National Institutes of Health (NIH) on R01s focused on nanomedicine in 2018 alone. In addition, the NIH created several special initiatives/programs, such as the National Cancer Institute (NCI) Alliance, to facilitate clinical translation of nanomedicines. Companies developing cancer nanomedicines raised diverse ranges of funds from venture capital, capital markets, and industry partnerships. In some cases, the development efforts resulted in regulatory approvals of cancer nanomedicines. In other cases, clinical failures and market pressure from improving standard of care products resulted in product terminations and business liquidation. Yet, recent approvals of nanomedicine products for orphan cancers and continuing development of nanoparticle based drugs for immune-oncology applications fuel continuing industrial and academic interest in cancer nanomedicines.