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Bedbugs are obligatory hematophagous (bloodsucking) insects. Most species only feed on humans when other prey are unavailable. They are normally out at night just before dawn, with a peak feeding period of about an hour before sunrise, but have been observed feeding during the day. Bedbugs are attracted to their hosts primarily by carbon dioxide, secondarily by warmth, and also by certain chemicals. They reach a detected host by crawling, or sometimes dropping from a height.

A bedbug pierces the skin of its host with two hollow feeding tubes. With one tube it injects its saliva, which contains anticoagulants and anesthetics, while with the other it withdraws the blood of its host. After feeding for about five minutes, the bug returns to its hiding place. The bites cannot usually be felt until some hours or even days later, as a dermatological reaction to the injected agents. The first indication of a bite usually comes from the desire to scratch the bite site. Because of their natural aversion for sunlight, bedbugs come out at night.

Although bedbugs can live for a year without feeding, they normally try to feed every five to ten days. When it's cold, bedbugs can live for about a year; at temperatures more conducive to activity and feeding, about 5 months.

At the 57th Annual Meeting of the Entomological Society of America in 2009, it was reported that newer generations of pesticide-resistant bedbugs in Virginia could survive only two months without feeding.

People react differently to bedbugs, and individual responses vary with factors including skin type, environment, and the species of bug. This also means the presence of itchy welts cannot be used as the only indicator of a presence. It is possible for an initial infestation within a household to be asymptomatic and go undetected. In some rare cases, allergic reactions to the bites may cause nausea and illness. In a large number of cases, estimated to be fifty percent of all people, there is no visible sign of bites whatsoever, greatly increasing the difficulty of identifying and eradicating infestations. People commonly respond to bed bug infestations and their bites with anxiety, stress, and insomnia. Development of refractory delusional parasitosis is common, as victims develop an overwhelming obsession with bedbugs. Individuals may also develop skin infections and scars from scratching the bedbug bite locations.