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"Let me say this about Nadine: Nadine had financial concerns that she kept from Bob," said the defence attorney, Mr Weitzman.
They led separate lives, Mr Weitzman said, with Mr Menendez often focused on helping his constituents from his seat in Washington.
"The government's allegations that the senator sold his office and his loyalty to this country are outrageously false," Mr Weitzman said. "Bob was doing his job, and he was doing it right."
Wednesday's opening arguments followed more than two days of jury selection. Twelve jurors and six alternatives were ultimately chosen, a group that includes an investment banker, a doctor and some therapists.
Mr Menendez has been charged with 18 criminal counts, including bribery, extortion, wire fraud, obstruction of justice and acting as a foreign agent.
Investigators executing a search warrant at his home in September found more than $480,000 (£380,000) in cash stuffed in envelopes and coats, and 13 gold bars worth over $100,000.
Agents also found other apparent gifts, including a Mercedes-Benz and a range of home furnishings.
Prosecutors say the items discovered were part of a scheme to aid the government of Egypt. They also allege Mr Menendez accepted bribes to use his influence to benefit Qatar.
Mr Menendez is on trial with Fred Daibes, a New Jersey real estate developer who allegedly delivered the gold and cash to the senator, and businessman Wael Hana, who allegedly brokered a deal between Mr Menendez and the Egyptian government. Both Mr Daibes and Mr Hana have also pleaded not guilty.