Cassandra Webb was born in Salem, Oregon. She is a paralyzed, blind, telepathic, clairvoyant, and precognitive mutant, allowing her to work as a professional medium. She was originally stricken with myasthenia gravis, a baffling disease that gradually erodes the central nervous system, and was connected to a life support system designed by her husband Jonathan Webb, which included a series of tubes shaped like a spider-web.She is also the grandmother of the fourth Spider-Woman, Charlotte Witter. During the "Gathering of the Five" ceremony, Webb was restored to youth and had her myasthenia gravis cured. At one point in time Webb served as a mentor of sorts to the third Spider-Woman, the young Mattie Franklin, though Franklin has retired as of late.

Madame Web has resurfaced and her psychic powers are intact after Decimation. However, since House of M (in which she did appear young) she seems to have regained her aged appearance, though the myasthenia gravis remains gone; this could indeed be taken as an effect of Decimation.

Madame Web is a mutant that possesses psychic sensory powers including telepathy, clairvoyance, prescience, precognition, and the ability to sense the presence of psionic powers in others. She can also perform psychic surgery and appear to others in spirit (astral) form. She has a gifted intellect.

Madame Web was a victim of myasthenia gravis, a debilitating disease which erodes the central nervous system. As a result, she was an invalid entirely dependent on external life support for survival. This is no longer the case as she was cured of the condition some time ago. She is also blind. Madame Web is cybernetically linked to a spider-web-like life support chair which attends to all of her bodily needs. However since she was cured, the chair might not serve the same functions it once did.

After the Gathering of the Five ceremony, she apparently has the gift of immortality.

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