Fjerde og siste gang Cary grant jobbet med Alfred Hitchcock var nettopp i North By Northwest, denne gnistrende gode spionthrilleren fra 1959. Grant spiller en reklamemann på Manhattan som plutselig blir kastet ut i en verden hvor spion står mot spion og ingen helt vet hvem som er fiende eller venn. Han blir selv kidnappet, anklaget for mord, jaktet på og - i en av filmhistoriens mest ikoniske scener - sprøytet ned av et småfly mens han er i fullt sprang over et jorde. North By Northwest er enkelt og greit et ekte mesterverk.

An ex-thief is accused of enacting a new crime spree, so to clear his name he sets off to catch the new thief, who’s imitating his signature style.

Cowboy Ross McEwen arrives in town. He asks the banker for a loan of $2000. When the banker asks about securing a loan that large, McEwen shows him his six-gun collateral. The banker hands over the money in exchange for an I.O.U., signed "Jefferson Davis". McEwen rides out of town and catches a train, but not before being bitten by a rattler. On the train, a nurse, Miss Hollister, tends to his wound. A posse searches the train, but McEwen manages to escape notice. However a mysterious Mexican has taken note of the cowboy, and that loudmouthed brat is still nosing around. Who will be the first to claim the reward for the robber's capture?

Questioned as a murder suspect, solid (but drunk) citizen Al Willis attacks his police questioners, is beaten, and swears vengeance against them. Next night, Lieut. Parks is murdered; Willis is the only suspect in the eyes of tough Chief Conroy, who pursues him doggedly despite lack of evidence. The obsessed Conroy is dismissed from the force, but continues to harass Willis, who flees to a sleazy town on the Mexican border. Of course, Conroy follows. But which is crazy, Conroy or Willis?