A spider bite is an injury resulting from a spider's forced interaction with other than prey organisms that can lead to medically significant complications. The most often seen cases of spider bites occur in humans and domesticated animals because of the cosmopolitan coexistence of both. A very small minority of spiders possess chelicerae strong enough to penetrate human skin, but this includes several of the species most commonly-encountered by humans. Although 98-99% of the bites thereby inflicted are harmless, more rarely, the symptoms can include necrotic wounds, systemic toxicity and, in some cases, death. Only some two hundred species in twenty genera (out of over 40,000 known species) are known to have serious, potentially lethal bites.

In almost all cases of biting, the chief concern is the spider's venom, although in some rare cases medically non-significant spiders can transmit infectious diseases. Spiders regarded as dangerous possess venom that is toxic to humans, in quantities that can be delivered by a single bite.

Only three genera of spiders are known to be non-venomous, i.e. lacking venom glands or any proper way to deliver it. They include the families Uloboridae, Holarchaeidae and Liphistiidae. These spiders, however, do possess fangs and can deliver sharp, unpleasant bites if disturbed. In addition, the fangs of Liphistiidae can often inflict infections spread through the skin, mostly due to their large size, which in theory could represent more danger than the bite of a non-lethal venomous spider species.

Experts on spider bites have noted that misdiagnoses of bites by both the general public and the medical community are quite common; many other conditions and diseases are confused with spider bites, sometimes preventing or delaying proper remedy, which can lead to deleterious outcomes. For example, there are numerous documented infectious and non-infectious conditions (including pyoderma gangrenosum, bacterial infections by Staphylococcus (including MRSA) and Streptococcus, herpes, diabetic ulcer, fungal infections, chemical burns, toxicodendron dermatitis, squamous cell carcinoma, localized vasculitis, syphilis, toxic epidermal necrolysis, sporotrichosis, and Lyme disease) exhibiting lesions that have been initially misdiagnosed as brown recluse spider bites by medical professionals. Many of these conditions are far more common and more likely to be the source of mysterious necrotic wounds, even in areas where recluses are present.

One subject that deserves in-depth study is the nature of the infections associated with spider bites. In many cases of suspected necrotising bites the symptoms are consistent with bacterial colonisation of the moribund (i.e. dead or dying) tissue, where the persistence of the festering is caused by bacterial action preventing healing that otherwise would have cleared up the problem in a few days. Untreated, such wounds sometimes fester for months, though, as noted above, it does not follow that every alarming case really is caused by a spider bite. Appropriate treatment for genuine necrotising bites however, is aggressive antibiotic injection at the first sign of infection, where antivenin might be unavailable or even hazardous.The use of the terms "poison" or "poisonous" in the context of spider bite is discouraged, as poison generally refers to substances which are harmful if absorbed through epithelial linings (e.g., eaten, or absorbed through the skin). The effect of eating spiders is, in general, unknown, but some spiders (such as tarantulas) are consumed as food

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