The show chronicles the adventures of an excessively helpful and enthusiastic dog named Ed who everyone adores, and his best friend, Doug the squirrel, whom everyone calls "Buddy" but nobody likes.

[4] The show follows two anthropomorphic animals, Ed, a cheerful, extroverted and idealistic but none-too-bright dog, and his polar opposite Buddy, a somewhat pessimistic but intelligent, introverted and realistic squirrel.

Despite their differences in both personality and lot in life, Ed and Buddy consider themselves best friends and have many adventures, and misadventures, in their town of Swellville (a play on Snellville), Canada, frequently confined (but not exclusively) to their suburban 333 Sweet Street.

Note: Every episode from "Rub My Ed for Luck" to "A Pox on Thee Now" was produced in 2008, yet aired in 2009 (with the exceptions of "Nightmare on Sweet Street" and "Cat Fright!").

In foreign countries, the show was also aired on Boomerang and Cartoon Network in the United Kingdom, and ABC Me in Australia.