In some ways, the practice of medicine between 1832 and 1849 seemed to be unraveling instead of progressing. There had been some limited licensing required to practice as a physician in the earlier era, but in 1844 New York (following several other states) removed all legal restrictions: anyone who claimed to be a doctor could practice. Those who could boast a degree from medical school were most competitive in the market place, but for a nominal fee and minimal study — in some cases, as little as six months of reading medical texts — one could earn a degree. This unregulated environment led to the proliferation of quacks and the marketing of questionable, "secret" remedies for illnesses.

These developments did little to mitigate the immediate impact of cholera. Most of the accepted and largely ineffective remedies that had been used in 1832, including calomel and bleeding, again formed the front line of defense. Beyond this, and reflecting the entrepreneurial ethos of mid-century America, any number of curatives were advertised in the nation's penny presses. And just as cholera had brought to the surface political and cultural conflicts, it also revealed rifts within the field of medical practice between those who favored "traditional" medicine and those who favored other approaches towards confronting disease. Practices such as homeopathy, in which doctors prescribed light doses of natural remedies to encourage the body to heal itself, and hydropathy, which advocated that patients be drenched, wrapped in wet towels, and urged to drink large quantities of water, gained popularity.

By 1849, however, most working in the medical field accepted the belief that cholera was "portable," although not contagious. Popular knowledge already seemed to accept this, as cities and nations braced themselves for invasion when adjacent locales were infected with cholera. A few medical researchers believed that microscopic organisms carried and transmitted the disease, but most believed that it was caused by an atmospheric shift that created a chemical reaction in the body. Either explanation could potentially be shaped to explain why cholera affected the poor most severely.

As ill-prepared as the medical field was to confront cholera in 1849, the outbreaks — more numerous than in 1832 — did provide ample opportunity for researchers to study the disease and its impact. Cholera was a presence in the United States and Europe through 1854, after which it disappeared for a dozen years. This persistence gave the London physician John Snow a chance to test a hypothesis that he first developed in 1849. Cholera, he believed, was transmitted via water contaminated by the waste of cholera victims. In 1854, Snow was able to trace the majority of incidences of cholera to those Londoners who drank water drawn from the lower Thames, rather than the upper Thames. By the time water reached the lower Thames, it had been contaminated with the city's sewage. Snow published his findings that same year, and immediately revolutionized understandings of cholera.