Given their reduced numbers, it is often forgotten that Lycans once proved a significant barrier as European settlers moved west across the continent. Although Lycans had existed in some number alongside American Indian populations, long-standing relationships, family ties, and religious pacts prevented these groups from fighting with any frequency. As a result, European settlers had to adapt, or draw on long-standing cultural tradition which harkened back to a time before the near extinction of the European werewolf in order to effectively combat the supernatural threat that Lycans posed.

Lycans are incredibly durable, possessing thick bones, a high pain tolerance, and incredibly rapid regenerative abilities. Even during the day, an un-turned Lyan can heal from catastrophic injuries with remarkable speed. However, they are far from indestructible.

Exsanguination is a feasible, though impractical, method of destroying a Lycan. Their extreme regenerative capabilities alongside mean that wounds which would otherwise cause rapid blood loss can heal themselves shut. They are also capable of producing red blood cells with great speed, meaning the quantity of blood lost must be significantly greater than that of a human to induce the same effects. That said, it is possible for Lycans to bleed to death, something which most commonly occurs during battles between opposing Lycans.

Curse-wounds are injuries inflicted by one Lycan upon another. Though the precise mechanism or purpose of such a weakness is unknown, Lycans heal much slower from injuries inflicted by other Lycans. (Please note: this applies only to wounds that break the skin, fractures and other internal injuries are, so far as can be ascertained, not affected.) If a Lycan is to bleed to death, it will likely be the result of mutual combat with one of their own kind. The reason for this adaptation is not known. Several theories exist, the most common of which is that it was a mutation of the curse which provided an advantage so extreme that all other variants of Lycan were driven to extinction. Another theory is that curse-wounds are meant to serve the opposite purpose, encouraging Lycans to cooperate as social animals rather than setting off on their own. Until such a time as the Blood Sickness is unraveled, the Bureau is unlikely to garner any answers to this question.

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Silver is the time-honored and traditional means to destroy a Lycan. Pure silver damages and destroys cursed blood, inhibiting the supernatural regenerative abilities of Lycans and burning when in contact with their flesh. As time has gone on, humans have used silver in various forms to destroy Lycans. Blades, spears, powders, and, most recently, ammunition made from silver are all effective means of destroying a Lycan.

Fire is also particularly effective against Lycans. Burns inflicted on a Lycan will often leave permanent scarring, and fire seems to be capable of overcoming the regenerative abilities of a Lycan, consuming the flesh as quickly as it restores itself.

If all else fails, dismemberment is always an option. A Lycan may heal an injury that would kill any human, but it will not restore its arm once it has been torn off, nor its head once it has been sliced free of its body.