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Khan started her film career starring in Javed Fazil's Bulandi in 1990.
Khan's early films included Zherilay, Ishq, Naag Devta, Pyar hi pyar, Sailab, Dil, Aag, Shama and Sahiba.
These were followed by films such as Hina, Anjuman, Chakuri, Chandni, Neelam and Insaniat. Later she appeared in Hathi Meray Sathi directed by Shameem Ara and in Rani Beti Raj Karegi directed by Altaf Hussain.
In 2002, Asif Ali Pota's Fire and Samina Peerzada's Shararat were released.
Most recently Reema Khan appeared alongsideMoammar Rana in the movie Love Mein Ghum which released on 31 August 2011 in Pakistan. The film reportedly was budgeted at 102 million and grossed 320 million. It also starred new actors Nabil Khan and Araida in leading roles.
She was the first Pakistani actress to be signed by Pepsi Co., Pakistan for their series of advertisements. She has now become an official partner of the Lahore zoo.
Reema Khan married American cardiologist surgeon S. Tariq Shahab on 16 November 2011 in Virginia. The nikkah took place at a local court in Virginia according to American law while Rukhsati took place on 20 November 2011. Her Walima was held in Pearl Continental Hotel Lahore on 27th May, 2012.
Her debut film as a director and producer, Koi Tujh Sa Kahan, was released in Pakistan and overseas. It went on to win the Best Film award at the Lux Style Awards in 2006. Khan won the award for the Best Actress and Best Director for the same film while Moammar Rana won the Best Actor Award.
Reema Khan also directed and produced Love Mein Ghum which released on 31 August 2011. The film was a huge critical and commercial success. It grossed over Rs. 320 million with a budget of Rs. 100 million. the film was declared super-hit.