The Supreme Court has ruled against Paul Lamb and Jane Nicklinson, of Melksham, who is campaigning on behalf of her late husband Tony, in their right-to-die legal battle.
It was announced today that justices, considering whether the legal ban on assisted suicide is incompatible with the European Convention on Human Rights, had decided against them by a seven-two majority.
Their ruling was delivered this morning after a hearing in December.
The action was brought by Jane Nicklinson, widow of locked-in syndrome sufferer Tony Nicklinson, of Melksham, who died in August 2012 after losing a High Court battle to end his life with a doctor's help, and Paul Lamb, who won the right to join the litigation to continue the case started by Mr Nicklinson.
She said today: "I am disappointed that we lost. But it is a very positive step. Parliament will have to discuss this.
"I think Tony would be very pleased at how far we have come."
Former builder and father-of-two Mr Lamb, of Leeds, wants a doctor to help him die. He is immobile except for limited movement in his right hand and has been in significant pain since a road accident in 1990. He had said a change in the law would "mean more to me than a million dollars".
Five of the nine justices concluded that the court had the "constitutional authority" to declare that a general prohibition on assisted suicide was incompatible with the human right to private and family life.
And two of those five said they would have made such a declaration.
Four justices said MPs were better placed to make such a compatibility assessment.
Justices also dismissed a separate challenge by another disabled man, after analysing guidance given by Alison Saunders, the director of public prosecutions (DPP).
That issue had been raised by a disabled man who was identified only as ''Martin''.
He argued that a ''policy statement'' setting out ''public interest factors to be considered in the exercise of discretion to prosecute'' was an unlawful interference with the right to respect for private and family life. His challenge was dismissed unanimously.
Sarah Wootton, chief executive of Dignity in Dying, said: "The Suicide Act is now over 50 years old and is out of touch with the problems facing dying Britons in the 21st century.
"Public opinion is resolutely in favour of change and now the Supreme Court has clearly indicated that it is only a matter of time before the law is reformed.
"If Parliament is unwilling to address the issue, then ultimately the courts will.
"The House of Lords has the opportunity to begin the process of reform when Lord Falconer's Assisted Dying Bill is debated by peers on 18 July.
"Ultimately a law passed by Parliament, with clear criteria and upfront safeguards, is preferable to decriminalisation by stages.
"Parliament can provide both greater choice and greater protection; we need a compassionate law that can safeguard choice for those at the end of life."
But earlier today Disability rights campaigner Baroness Tanni Grey-Thompson called for the law on assisted suicide to remain unchanged. The former wheelchair athlete said the law as it stands offers "very powerful judicial discretion" while preventing people from being coerced into taking their own lives.
"It is very hard not to be moved when you see some very tragic cases like those being reported today but the law is there to protect us all, it is there to protect vulnerable people, elderly people, who could potentially be coerced into thinking that this is the only option that they have," she told BBC Breakfast.
"If you look at Washington state, which is one of the jurisdictions that has an assisted suicide law, 61 per cent of people who have gone for assisted suicide say they have done it because they feel a burden to their family. It should be about care not about being a burden."